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Articles 1 - 30 of 34
Full-Text Articles in Developmental Neuroscience
The Genomics Of Autism-Related Genes Il1rapl1 And Il1rapl2: Insights Into Their Cortical Distribution, Cell-Type Specificity, And Developmental Trajectories, Jacob Weaver
MUSC Theses and Dissertations
Neuropsychiatric disorders have a significant impact on modern society. These disorders affect a large percentage of the population: schizophrenia has a world-wide prevalence of 1% and autism spectrum disorders (ASD) affects 1 in 59 school-aged children in the US. There is substantial evidence that most neuropsychiatric disorders have a genetic component. Thus, with the advent of high throughput sequencing much effort has gone into identifying genetic variants associated with these disorders. The emerging picture from these studies is a complex one where hundreds of genes with small effects interact with a varied landscape of common variants to result in disease. …
Med12 Is A Critical Regulator Of Neural Crest Lineage And Nervous System Myelination, Fatma Betul Aksoy Yasar
Med12 Is A Critical Regulator Of Neural Crest Lineage And Nervous System Myelination, Fatma Betul Aksoy Yasar
Dissertations & Theses (Open Access)
The Mediator complex (MED) is a multi-subunit protein complex integral to the eukaryotic transcription machinery. MED12 is a Cdk8- regulatory kinase module subunit directly implicated in human disease and is genetically altered in neurological disease and cancer. Numerous attempts at generating an in vivo system to study the role of Med12 failed due to embryonic lethality associated with germline or developmental disruption of Med12 gene. To understand the cellular and molecular processes associated with its role in disease, we generated multiple mouse models with targeted depletion of MED12 in distinct cellular lineages. Our genetically engineered models with induced and conditional …
Identification Of Dna Methylation Episignatures For Classification And Phenotype/Genotype Correlation In Mendelian Neurodevelopmental Disorders, John Reilly
Electronic Thesis and Dissertation Repository
ABSTRACT: Diagnosis for neurodevelopmental disorders poses numerous challenges, related to the lack of specific findings and limited understanding of clinical impact of the majority of genetic variation. Epigenomics mechanisms involve chemical modifications in DNA that involve a range of cellular mechanisms. DNA methylation is an epigenetic mechanism involving addition and removal of methyl groups to cytosine residues. These methylation signals form episignatures; patterns of methylation that can be used as biomarkers capable of differentiating neurodevelopmental disorders. EpiSigns have enabled molecular diagnosis of a number of genetic conditions, classification of variants of unknown significance, and provided insights into the pathophysiology of …
Examining Development And Function Of Pretectal Visual Neural Circuits In Gs Homeobox 1 Mutant Zebrafish, Alexandra Rose Schmidt
Examining Development And Function Of Pretectal Visual Neural Circuits In Gs Homeobox 1 Mutant Zebrafish, Alexandra Rose Schmidt
Graduate Theses, Dissertations, and Problem Reports
Brain development requires a coordinated genetic code to regulate initial cell identity determination, migration, and connectivity, to establish function of neural circuits. Independent neural circuits underlie our ability to produce both complex and innate behavioral responses to sensory stimuli that are often conserved across vertebrate organisms. Sensory processing disruptions are associated with several neurodevelopmental disorders (NDDs). Therefore, gene mutations altering neurodevelopment can lead to changes influencing structure and function of individual neural circuits, causing behavioral deviations in sensory responsiveness. Crucial gene networks that define functional properties of sensory domains are often explored using non-mammalian vertebrate models, such as the zebrafish. …
Having A High-Activity Catechol-O-Methyltransferase Allele Is Associated With Elevated Anxiety And Lower Salivary Dehydroepiandrosterone But Also Lower Alpha Amylase In Children With Chromosome 22q11.2 Deletion Syndrome., Jessie Beebe
University of New Orleans Theses and Dissertations
Chromosome 22q11.2 deletion syndrome (22q11.2DS) results from a hemizygous deletion located on the long arm of chromosome 22. The most common deletion sizes affect between 30 and 90 genes. Individuals with 22q11.2DS may develop serious developmental and psychiatric disorders. The phenotype is highly variable, however, and may be influenced by allelic variation of the retained copies of genes covered by the deletion. I set out to examine the effects of two genes, catechol-O-methyltransferase (COMT) and proline dehydrogenase (PRODH), in relation to anxiety in children and adolescents with 22q11.2DS. Individuals with the major COMT allele (higher activity) have significantly higher anxiety …
Biallelic Variants In Pcdhgc4 Cause A Novel Neurodevelopmental Syndrome With Progressive Microcephaly, Seizures, And Joint Anomalies, Maria Iqbal, Reza Maroofian, Büşranur Çavdarlı, Florence Riccardi, Michael Field, Siddharth Banka, Dalal K. Bubshait, Yun Li, Jozef Hertecant, Shahid Mahmood Baig
Biallelic Variants In Pcdhgc4 Cause A Novel Neurodevelopmental Syndrome With Progressive Microcephaly, Seizures, And Joint Anomalies, Maria Iqbal, Reza Maroofian, Büşranur Çavdarlı, Florence Riccardi, Michael Field, Siddharth Banka, Dalal K. Bubshait, Yun Li, Jozef Hertecant, Shahid Mahmood Baig
Department of Biological & Biomedical Sciences
Purpose: We aimed to define a novel autosomal recessive neurodevelopmental disorder, characterize its clinical features, and identify the underlying genetic cause for this condition.
Methods: We performed a detailed clinical characterization of 19 individuals from nine unrelated, consanguineous families with a neurodevelopmental disorder. We used genome/exome sequencing approaches, linkage and cosegregation analyses to identify disease-causing variants, and we performed three-dimensional molecular in silico analysis to predict causality of variants where applicable.
Results: In all affected individuals who presented with a neurodevelopmental syndrome with progressive microcephaly, seizures, and intellectual disability we identified biallelic disease-causing variants in Protocadherin-gamma-C4 (PCDHGC4). Five variants were …
The Neurological Asymmetry Of Self-Face Recognition, Aleksandra Janowska, Brianna Balugas, Matthew Pardillo, Victoria Mistretta, Katherine Chavarria, Janet Brenya, Taylor Shelansky, Vanessa Martinez, Kitty Pagano, Nathira Ahmad, Samantha Zorns, Abigail Straus, Sarah Sierra, Julian Keenan
The Neurological Asymmetry Of Self-Face Recognition, Aleksandra Janowska, Brianna Balugas, Matthew Pardillo, Victoria Mistretta, Katherine Chavarria, Janet Brenya, Taylor Shelansky, Vanessa Martinez, Kitty Pagano, Nathira Ahmad, Samantha Zorns, Abigail Straus, Sarah Sierra, Julian Keenan
Department of Biology Faculty Scholarship and Creative Works
While the desire to uncover the neural correlates of consciousness has taken numerous directions, self-face recognition has been a constant in attempts to isolate aspects of self-awareness. The neuroimaging revolution of the 1990s brought about systematic attempts to isolate the underlying neural basis of self-face recognition. These studies, including some of the first fMRI (functional magnetic resonance imaging) examinations, revealed a right-hemisphere bias for self-face recognition in a diverse set of regions including the insula, the dorsal frontal lobe, the temporal parietal junction, and the medial temporal cortex. In this systematic review, we provide confirmation of these data (which are …
The Role Of Placental Genes On Intellectual Disability And Developmental Delay, Maedot A. Yidenk
The Role Of Placental Genes On Intellectual Disability And Developmental Delay, Maedot A. Yidenk
Dissertations, Theses, and Capstone Projects
The complex interaction between gene expressions and environmental factors plays a key role in the pathogenesis of various diseases, including neurodevelopmental disorders (Lenroot & Giedd, 2008). This study aimed to evaluate first, the magnitude of association between placental gene Methyl-CpG Binding Protein 2 (MeCP2) and intellectual disability (ID) in the offspring and second, the synergy between placental gene Forkhead box protein 1(FOXP1) and developmental delay (DD) in the offspring. We focused on assessing two specific paradigms, i) placental gene expressions of MeCP2 among children that have ID vs. children without ID; and ii) placental gene expression of …
The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan
The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan
Honors Scholar Theses
The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …
The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan
The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan
University Scholar Projects
The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …
Influence Of Myelin-Associated Glycoprotein On Axon Subtype Specific Sheath Targeting, Nazmus Sakib Khan
Influence Of Myelin-Associated Glycoprotein On Axon Subtype Specific Sheath Targeting, Nazmus Sakib Khan
Ramaley Celebration
During the development of the Central Nervous System, oligodendrocytes wrap axons with myelin, which is necessary for rapid, efficient nerve impulse propagation. For reasons unknown, oligodendrocytes direct myelin to certain subtypes of axons, leaving others incompletely myelinated, or even totally unmyelinated. Previous studies demonstrated mice harboring Mag mutations showed improper sheath targeting of myelin to axons indicating that MAG is a possible facilitator of axon-glia communication.
In the present study, we tested the hypothesis that loss of mag decreases the proportion of myelin directed towards specific axon subtypes. To test this, we perturbed Mag function in zebrafish embryos using knockdown …
The Influence Of Autism Linked Gene Topoisomerase 3b (Top3b) On Neural Development In Zebrafish, Sydney Doolittle
The Influence Of Autism Linked Gene Topoisomerase 3b (Top3b) On Neural Development In Zebrafish, Sydney Doolittle
Honors College Theses
Autism Spectrum Disorder is a class of developmental disabilities characterized by a spectrum of social, communication, and behavioral impairments in affected individuals. Studies have shown these defects stem from abnormal brain development during critical periods during early development. The underlying genetic cause of these impairments is not well understood but is believed to be a combination of a complex pairing of genetic and environmental factors. One of the genetic factors that has been recognized to influence the phenotypic symptoms of ASD is the enzyme topoisomerase 3β (top3β.) Topoisomerases are responsible for the prevention of supercoiling during DNA replication. Top3β is …
A Pathogenic Ufsp2 Variant In An Autosomal Recessive Form Of Pediatric Neurodevelopmental Anomalies And Epilepsy, Min Ni, Bushra Afroze, Chao Xing, Chunxiao Pan, Yanqiu Shao, Ling Cai, Brandi L. Cantarel, Jimin Pei, Nick V. Grishin, Stacy Hewson
A Pathogenic Ufsp2 Variant In An Autosomal Recessive Form Of Pediatric Neurodevelopmental Anomalies And Epilepsy, Min Ni, Bushra Afroze, Chao Xing, Chunxiao Pan, Yanqiu Shao, Ling Cai, Brandi L. Cantarel, Jimin Pei, Nick V. Grishin, Stacy Hewson
Department of Paediatrics and Child Health
Purpose: Neurodevelopmental disabilities are common and genetically heterogeneous. We identified a homozygous variant in the gene encoding UFM1-specific peptidase 2 (UFSP2), which participates in the UFMylation pathway of protein modification. UFSP2 variants are implicated in autosomal dominant skeletal dysplasias, but not neurodevelopmental disorders. Homozygosity for the variant occurred in eight children from four South Asian families with neurodevelopmental delay and epilepsy. We describe the clinical consequences of this variant and its effect on UFMylation.
Methods: Exome sequencing was used to detect potentially pathogenic variants and identify shared regions of homozygosity. Immunoblotting assessed protein expression and post-translational modifications in patient-derived fibroblasts. …
Estrogen Disruption Of Hypothalamic Neural Activity, Princess Dickson
Estrogen Disruption Of Hypothalamic Neural Activity, Princess Dickson
Cal Poly Humboldt theses and projects
The brain is highly dependent on the endocrine system for proper neurodevelopment, as it plays a key role in many biological processes. Bisphenol A is a chemical found in plastics that has the potential to mimic the effects of Estrogen in the body, at least weakly. People interact with plastic that contains BPA regularly, and people are at risk for exposure even before being born. The abundance of BPA, along with other exogenous estrogens, makes examining the relationship between early exposure and changes in brain activity imperative. The current study aims to establish a relationship between disrupted estrogen function and …
Gene Regulation And Cell Fate Choice In The Developing Vertebrate Retina, Sruti Patoori
Gene Regulation And Cell Fate Choice In The Developing Vertebrate Retina, Sruti Patoori
Dissertations, Theses, and Capstone Projects
The diverse neuronal cell types in the vertebrate retina all originate from multipotent retinal progenitor cells (RPCs). These undergo a series of molecular changes driven by developmental gene regulatory networks (GRNs) as they divide to generate RPCs which are more restricted in their potential fates. It is crucial to understand these GRNs and changes to gene expression in order to understand how cell identity is established during retinal development. In particular, the GRN that promotes the development of cone photoreceptors and horizontal cells is not well-defined. This work focuses on two approaches to further elucidate the components of this regulatory …
Thyroxine-Dependent And -Independent Effects On Premature Aging And Myelination In Atrx Mutant Mice, Megan E. Rowland
Thyroxine-Dependent And -Independent Effects On Premature Aging And Myelination In Atrx Mutant Mice, Megan E. Rowland
Electronic Thesis and Dissertation Repository
ATRX is an ATP-dependent chromatin remodeler required to safeguard genomic integrity. Conditional deletion of Atrx in the mouse embryonic forebrain and anterior pituitary in AtrxFoxg1Cre mice phenocopies mouse models of progeria which display increased DNA damage, coupled with reduced lifespan, growth and subcutaneous fat. These mice also have severely low circulating levels of insulin like growth factor 1 (IGF-1) and (T4) which have been reported in models of premature aging. Based on evidence that Igf1 is activated by the ligand-bound thyroid hormone receptor, I tested whether T4 supplementation could restore IGF-1 levels and ameliorate premature aging phenotypes in Atrx …
Notch Inhibitors And The Bet Inhibitor Jq-1 Decrease The Growth Of Primary Tumor Cells Derived From A Novel Mouse Model Of C11orf95-Rela Induced Brain Tumor, Ericka Randazzo, Jesse Dunnack, Justin Fang, Joseph Loturco Phd
Notch Inhibitors And The Bet Inhibitor Jq-1 Decrease The Growth Of Primary Tumor Cells Derived From A Novel Mouse Model Of C11orf95-Rela Induced Brain Tumor, Ericka Randazzo, Jesse Dunnack, Justin Fang, Joseph Loturco Phd
University Scholar Projects
Brain tumors are the most common childhood solid malignancy, and because of remarkable advances in treating many cancers outside of the brain, they have become the leading cause of cancer mortality in children. Ependymomas are a class of brain tumors which can be further subdivided into three groups based upon their location and genetic features. Of the three classes, supratentorial ependymomas are the only subgroup known to be marked by an oncogenic driver gene, which consists of a fusion mutation between the C11orf95 and RELA genes. C11orf95-RELA positive tumors are the most aggressive and lethal of …
Circadian Rhythmicity And Neurodevelopment Of Disco And Grim Mutations In Drosophila Melanogaster, John Patrick Story
Circadian Rhythmicity And Neurodevelopment Of Disco And Grim Mutations In Drosophila Melanogaster, John Patrick Story
EURēCA: Exhibition of Undergraduate Research and Creative Achievement
The death gene grim and its pathway for apoptosis has been studied extensively in Drosophila Melanogaster. The effects of grim mutations on circadian neurodevelopment and locomotor assays have yet to be investigated. Mutations in the gene disconnected (disco) has been shown to disrupt the normal development of the circadian circuitry, specifically the small ventro-lateral neurons (s-LNv’s). Which has shown to severely decrease rhythmicity during free-running periods. Alternatively, we have observed an increase in rhythmicity during free-running periods in grim mutations. Our goal is to investigate the neurodevelopment of the circadian circuitry and their associated locomotor activities in these Drosophila mutations.
Glial Cell Expansion And Intercellular Signaling In The Developing Medial Nucleus Of The Trapezoid Body (Mntb), Ashley N. Brandebura
Glial Cell Expansion And Intercellular Signaling In The Developing Medial Nucleus Of The Trapezoid Body (Mntb), Ashley N. Brandebura
Graduate Theses, Dissertations, and Problem Reports
Neural circuit formation is a complex process involving coordinated communication between neurons, glia and vascular-associated cells (VACs). Each cell type is responsible for a unique transcriptional and translational contribution to tissue maturation. Deciphering the intercellular signaling patterns which guide neural circuit formation during normal development is thus an essential step in understanding which components of neural circuit formation go awry in neurodevelopmental disorders. The medial nucleus of the trapezoid body (MNTB), located in the auditory brainstem, was used as a model system to study the dynamics of neural circuit formation because it contains a mostly homogeneous population of postsynaptic neurons …
Underlying Contribution Of Executive Functioning To Cognition And Academic Achievement In Individuals With Dystrophinopathy, Robert Fee
Dissertations, Theses, and Capstone Projects
Dystrophinopathy is a genetic disorder that results in the lack of or abnormal expression of the protein dystrophin. It is a disorder that alters cell structure and function, impacts the developing brain and brain function, presents with multi-domain cognitive deficits, and influences both mood and behavior. Cognitive impairments appear to be more localized to specific areas of functioning rather than a global deficit; however, deficits have been identified across multiple cognitive domains including language and aspects of executive functioning. A careful examination of the cognitive phenotype and its association to mutations affecting CNS isoforms is necessary to clarify the neuropsychological …
The Ush2a Gene: An Analysis Of Ultrasonic Vocalizations In A Mouse Model Of Usher Syndrome Type 2, Kiana R. Akhundzadeh
The Ush2a Gene: An Analysis Of Ultrasonic Vocalizations In A Mouse Model Of Usher Syndrome Type 2, Kiana R. Akhundzadeh
Honors Scholar Theses
Usher syndrome type 2 is a complex autosomal recessive genetic disorder that is characterized by moderate to severe congenital sensorineural hearing loss, the onset of retinitis pigmentosa in the second decade of life, and in some cases, vestibular dysfunction. Mutations in the USH2A gene account for 85% of cases of type 2. The USH2A gene is responsible for encoding the protein usherin, which has an important role in the development and function of inner ear hair cells and retinal photoreceptors. Until recently, it has been believed that carriers of the USH2A mutation were phenotype free. However, recent data has suggested …
Jennifer Maurer Phd Thesis.Pdf, Jennifer Maurer
Jennifer Maurer Phd Thesis.Pdf, Jennifer Maurer
Jennifer Maurer
Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, Aniruddho Chokroborty-Hoque
Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, Aniruddho Chokroborty-Hoque
Electronic Thesis and Dissertation Repository
Maternal alcohol consumption during pregnancy results in a spectrum of behavioural and cognitive deficits collectively known as Fetal Alcohol Spectrum Disorders (FASD). Currently, little is know about if and how the external environment may modulate these deficits. I have used C57BL/6 mice to study this interaction between prenatal alcohol exposure and the postnatal environment. Alcohol exposure during synaptogenesis produces high levels of anxiety-like traits and decreased memory performance. Alcohol-exposed mice (and matched unexposed controls) were put in 'environmentally-enriched' conditions of voluntary exercise, physical activities and cognitive stimulation to ascertain the effects of a positive postnatal environment. The results show that …
Molecular And Pathological Analyses Of Three New Mouse Mutations That Affect Ear Development And Function, Cong Tian
Electronic Theses and Dissertations
This dissertation presents three new mouse models that help to study the functions of Enpp1, Atp6v1b1, and Tbx1 for ear development and function. asj (aging with stiffened joints) carries a missense mutation in the mouse Enpp1 gene. Enpp1 encodes the enzyme ENPP1 that regulate soft-tissue calcification and bone mineralization, and is associated with generalized arterial calcification of infancy and hypophosphatemic rickets in human patients. asj mutant mice show severe middle ear infection and tissue calcification, which provide a new mouse model to study otitis media and tympanoscleorosis. Atp6v1b1 encode a protein that is a subunit of the V-ATPase …
Ephrin Receptors, Aiy Interneuron Physiology, And Behavior, Tyler Hill
Ephrin Receptors, Aiy Interneuron Physiology, And Behavior, Tyler Hill
Master of Science in Integrative Biology Theses
In order to survive, an organism must be able to receive, integrate, and respond to sensory stimuli. However, the cellular basis of sensory perception and response is difficult to study in complex animals such as humans, and is therefore poorly understood. The nematode Caenorhabditis elegans is a relatively simple organism yet displays many distinct behaviors, making it an ideal system to understand the relationship between gene function, cell shape, cell physiology, and behavioral output. Much of the thermosensory and chemosensory information that the nematode receives from its sensory neurons is processed via a pair of interneurons called AIYL and AIYR. …
Modeling 3d Retinogenesis In Mouse Embryonic Stem Cells Following Crispr-Mediated Crx Knockdown, Pooja Prasad
Modeling 3d Retinogenesis In Mouse Embryonic Stem Cells Following Crispr-Mediated Crx Knockdown, Pooja Prasad
Dissertations, Masters Theses, Capstones, and Culminating Projects
An emerging technology known as three-dimensional (3D) tissue engineering has allowed scientists to mimic tissues found in vivo. Previous studies indicate that it is possible to differentiate dissociated mouse embryonic stem cells (mESCs) into 3D retinal tissues in vitro (Bertacchi, 2015; Eiraku, 2012). The newly differentiated retinal tissues are said to encompass all of the major components found in retinal tissues. The generation of in vitro 3D tissues holds great potential in terms of patient-specific disease modeling. Although various diseases have been well-studied in animal models, there are limitations with regards to patient-specificity. The generation of animal models to study …
Pigment Dispersing Factor: Transcriptional Regulation And Its Role In Metabolism In Drosophila Melanogaster, Sudershana Nair
Pigment Dispersing Factor: Transcriptional Regulation And Its Role In Metabolism In Drosophila Melanogaster, Sudershana Nair
Doctoral Dissertations
Almost all living organisms have circadian clocks coordinating physiology and behavior, and an innate molecular clock drives rhythmic changes by integrating environmental and metabolic stimuli to generate 24 hour timing. Drosophila melanogaster has proved to be an excellent model organism with a well-characterized circadian clock and the neural circuits underlying clock have been intensely investigated. The neuropeptide pigment-dispersing factor (PDF) plays an essential role in maintaining circadian rhythmicity and synchronizes circadian clock neurons. However, the regulation of Pdf has been a black box with no known protein identified that directly regulates it, and its role in metabolism hasn’t been looked …
The Role Of Daf-19 In Non-Ciliated Neurons: How Is Neural Development Regulated By Different Daf-19 Isoforms?, Zabdiel Ek Vazquez
The Role Of Daf-19 In Non-Ciliated Neurons: How Is Neural Development Regulated By Different Daf-19 Isoforms?, Zabdiel Ek Vazquez
Lawrence University Honors Projects
A degenerative disease-like phenotype, specifically reduction in synaptic protein levels in adult worms, is correlated with loss-of-function of the only RFX transcription factor gene, daf-19, in C. elegans. This gene encodes four known transcription factor isoforms, two of which are correlated with particular functions. The DAF-19C isoform activates genes responsible for cilia development, while DAF-19M is needed for cilia specification in males. A comparison of the transcriptome of daf-19 null and isogenic wild type adult worms suggests both positive and negative regulation of gene expression is correlated with the presence of DAF-19 proteins. We have assessed DAF-19 regulation …
Ethanol Exposure During Synaptogenesis In A Mouse Model Of Fetal Alcohol Spectrum Disorders: Acute And Long-Term Effects On Gene Expression And Behaviour, Morgan L. Kleiber
Ethanol Exposure During Synaptogenesis In A Mouse Model Of Fetal Alcohol Spectrum Disorders: Acute And Long-Term Effects On Gene Expression And Behaviour, Morgan L. Kleiber
Electronic Thesis and Dissertation Repository
Alcohol is a neuroactive molecule that is able to exert variable and often detrimental effects on the developing brain, resulting in a broad range of physiological, behavioural, and cognitive phenotypes that characterize ‘fetal alcohol spectrum disorders’ (FASD). Factors affecting the manifestation of these phenotypes include alcohol dosage, timing of exposure, and pattern of maternal alcohol consumption; however, the biological processes that are vulnerable to ethanol at any given neurodevelopmental stage are unclear, as is how their disruption results in the emergence of specific pathological phenotypes later in life.
The research included in this thesis utilizes a C57BL/6J (B6) mouse model …
Developmental Decline In Neuronal Regeneration By The Progressive Change Of Two Intrinsic Timers, Yan Zou, Hui Chiu, Anna Zinovyeva, Victor Ambros, Chiou-Fen Chuang, Chieh Chang
Developmental Decline In Neuronal Regeneration By The Progressive Change Of Two Intrinsic Timers, Yan Zou, Hui Chiu, Anna Zinovyeva, Victor Ambros, Chiou-Fen Chuang, Chieh Chang
Victor R. Ambros
Like mammalian neurons, Caenorhabditis elegans neurons lose axon regeneration ability as they age, but it is not known why. Here, we report that let-7 contributes to a developmental decline in anterior ventral microtubule (AVM) axon regeneration. In older AVM axons, let-7 inhibits regeneration by down-regulating LIN-41, an important AVM axon regeneration-promoting factor. Whereas let-7 inhibits lin-41 expression in older neurons through the lin-41 3' untranslated region, lin-41 inhibits let-7 expression in younger neurons through Argonaute ALG-1. This reciprocal inhibition ensures that axon regeneration is inhibited only in older neurons. These findings show that a let-7-lin-41 regulatory circuit, which was previously …